2023-10-12 23:28:03
October 13, 2023, reading time: 4 minutes.
Microbial toxins: One of the causes of Parkinson’s may lie in our intestines. Some microorganisms there produce substances that can damage our nerve cells, as researchers have discovered. According to this, a metabolic product of the bacterium Streptomyces venezuelae primarily destroys the neurons that produce dopamine and triggered Parkinson-like symptoms in animal experiments. This sheds new light on the role of the microbiome in Parkinson’s and other neurodegenerative diseases.
Parkinson’s is a neurodegenerative disease in which nerve cells are progressively destroyed because certain proteins accumulate and clump together. Neurons that produce dopamine are particularly affected. The causes of Parkinson’s have only been partially researched. Although genetic changes are known to be a trigger for the disease, in 90 percent of cases Parkinson’s symptoms occur without a clear genetic origin. In addition, age is a significant risk factor for Parkinson’s, but it is unclear which aging processes are involved.
Scientists suspect that environmental factors might also play a role in the development of the disease. For example, it is being investigated whether pesticides from agriculture and industrial chemicals found in the environment are linked to neurodegeneration. Viruses are also discussed as possible triggers.
What role does intestinal flora play in Parkinson’s?
However, the intestinal flora and the human microbiome as a whole are also suspected. Studies show that Parkinson’s patients have a different combination of microbes in their intestines than healthy people. There is also evidence that some metabolic products of the microorganisms, so-called metabolites, selectively attack dopamine-producing neurons.
A team led by Anna-Katharina Ückert from the University of Konstanz has now examined such a metabolic product of the bacterium Streptomyces venezuelae in more detail. Although this bacterium lives in the soil, it may have similar metabolic pathways and products as microorganisms in our bodies. The researchers hope that the experiments will provide information regarding the type of harmful metabolite and its synthesis route so that they can compare this with the human microbiome.
Bacterial metabolite in the test
For their study, the team first isolated the bacterium’s metabolite from Streptomyces venezuelae extracts in several purification steps and identified it using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR). For further tests, the researchers also chemically produced the identified substance.
The scientists then added the isolated and synthetically recreated substance in the laboratory to human dopamine-producing neurons, other human nerve cells and non-neuronal human cells. They then observed whether the brain cells deformed or died. Ückert and her colleagues also tested whether various natural inhibitors and antioxidants prevented cell damage.
Bacterium produces the toxin aerugin
The experiments revealed that the metabolite is a combination of two substances, aerugin and aeruginol, two 2-hydroxyphenyl-thiazoline compounds that also occur in the human microbiome and in several pathogens. In the study, both substances destroyed human nerve cells, especially dopamine-producing neurons. “Normal” cells, however, remained intact. Since Aerugin was more toxic than Aeruginol, the researchers only carried out further tests with this active ingredient.
Similar to Parkinson’s disease, neurodegeneration triggered by aerugin led to the death of neurons in the experiments. However, the effect on the tested cell lines might be reversed by adding certain antioxidants and iron inhibitors. The researchers conclude that aerugin is only toxic to the cells in combination with iron.
Toxic effects also demonstrated in roundworms
But what consequences do the identified toxins of Streptomyces venezuelae have in a living organism? To find out, the researchers also exposed nematodes (Caenorhabditis elegans) to the bacterial metabolite aerugin and examined its effect on the model organism’s nervous system.
In fact, following contact with the bacterial toxin, the worms showed movement difficulties and specific neuronal patterns similar to those of human Parkinson’s patients. Further experiments with stained neurons showed that the toxin also specifically attacked the dopamine-producing nerve cells in roundworms.
Conclusions regarding triggers for neurodegenerative diseases
The study thus offers a new perspective on the triggers of Parkinson’s. “Our research establishes a tangible link between a specific bacterial metabolite and symptoms similar to Parkinson’s. It is a further step towards understanding how our environment, down to the microbes around us, might influence the onset or progression of such diseases,” says co-senior author Marcel Leist from the University of Konstanz.
At the same time, the discoveries raise new questions: Could other microbial substances also influence neurodegenerative diseases such as Parkinson’s? How do these toxins interact with our neurons? And can knowledge of them and possible “antidotes” lead to new treatments or preventive measures? To answer this, further research is needed.
“Although our study is just a beginning, it is a promising step towards unraveling the molecular causes of Parkinson’s and other neurodegenerative diseases,” says co-senior author Thomas Böttcher from the University of Vienna. (Environment International, 2023, doi: 10.1016/j.envint.2023.108229)
Sources: University of Vienna, University of Konstanz
October 13, 2023 – Claudia Krapp
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